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Translational Research: the Journal of Laboratory and Clinical Medicine

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https://www.readbyqxmd.com/read/29421522/prostaglandin-endoperoxide-synthase-2-cyclooxygenase-2-a-complex-target-for-colorectal-cancer-prevention-and-therapy
#1
REVIEW
Roberto Benelli, Roberta Venè, Nicoletta Ferrari
A plentiful literature has linked colorectal cancer (CRC) to inflammation and prostaglandin-endoperoxide synthase (PTGS)2 expression. Accordingly, several nonsteroidal antiinflammatory drugs (NSAIDs) have been tested often successfully in CRC chemoprevention despite their different ability to specifically target PTGS2 and the low or null expression of PTGS2 in early colon adenomas. Some observational studies showed an increased survival for patients with CRC assuming NSAIDs after diagnosis, but no clinical trial has yet demonstrated the efficacy of NSAIDs against established CRC, where PTGS2 is expressed at high levels...
February 2, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29432720/exosomes-and-regenerative-medicine-state-of-the-art-and-perspectives
#2
REVIEW
Hui Jing, Xiaomin He, Jinghao Zheng
Exosomes have attracted the attention of the scientific community in recent years due to their widespread distribution, their possible functions as biomarkers of disease, and their great potential to be applied as therapeutic agents. Exosomes carry proteins and nucleic acids that can facilitate their uptake by distant target cells through endocytosis, such that exosomes could be targeted to a specific cell or cells to enhance or interfere with specific biological processes. This review will mainly focus on their roles in tissue repair and regenerative processes...
January 31, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29421523/maraviroc-improves-hepatic-triglyceride-content-but-not-inflammation-in-a-murine-nonalcoholic-fatty-liver-disease-model-induced-by-a-chronic-exposure-to-high-fat-diet
#3
Laura Pérez-Martínez, Laura Ochoa-Callejero, Susana Rubio-Mediavilla, Judit Narro, Iván Bernardo, José-Antonio Oteo, José-Ramón Blanco
Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in the general population. Its severity ranges from simple steatosis to cirrhosis. C-C chemokine ligand type 5 or RANTES plays an important role in the progression of hepatic inflammation and fibrosis. Our objective was to examine the preventive and therapeutic effects of maraviroc (MVC), a C-C chemokine receptor 5 antagonist, on liver pathology in an NAFLD mouse model. A total of 60 male C57BL/6 mice were randomly assigned to 1 of 4 groups: (1) high-fat diet (HFD) group or control group, (2) preventive group (HFD group plus MVC in drinking water since the beginning of the study), (3) early-therapeutic group (HFD group plus MVC in drinking starting at week 24 of the study), and (4) late-therapeutic group (HFD group plus MVC in drinking water starting at week 36 of the study)...
January 31, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29360430/image-analysis-and-machine-learning-for-detecting-malaria
#4
REVIEW
Mahdieh Poostchi, Kamolrat Silamut, Richard Maude, Stefan Jaeger, George Thoma
Malaria remains a major burden on global health, with roughly 200 million cases worldwide and more than 400,000 deaths per year. Besides biomedical research and political efforts, modern information technology is playing a key role in many attempts at fighting the disease. One of the barriers toward a successful mortality reduction has been inadequate malaria diagnosis in particular. To improve diagnosis, image analysis software and machine learning methods have been used to quantify parasitemia in microscopic blood slides...
January 12, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29352978/use-of-multimodality-imaging-and-artificial-intelligence-for-diagnosis-and-prognosis-of-early-stages-of-alzheimer-s-disease
#5
REVIEW
Xiaonan Liu, Kewei Chen, Teresa Wu, David Weidman, Fleming Lure, Jing Li
Alzheimer's disease (AD) is a major neurodegenerative disease and the most common cause of dementia. Currently, no treatment exists to slow down or stop the progression of AD. There is converging belief that disease-modifying treatments should focus on early stages of the disease, that is, the mild cognitive impairment (MCI) and preclinical stages. Making a diagnosis of AD and offering a prognosis (likelihood of converting to AD) at these early stages are challenging tasks but possible with the help of multimodality imaging, such as magnetic resonance imaging (MRI), fluorodeoxyglucose-positron emission topography (PET), amyloid-PET, and recently introduced tau-PET, which provides different but complementary information...
January 10, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29351829/inhibition-of-dynamin-related-protein-1-has-neuroprotective-effect-comparable-with-therapeutic-hypothermia-in-a-rat-model-of-cardiac-arrest
#6
Peng Wang, Yi Li, Zhengfei Yang, Tao Yu, Guanghui Zheng, Xiangshao Fang, Zitong Huang, Longyuan Jiang, Wanchun Tang
Dynamin-related protein 1 (Drp1) regulates mitochondrial fission, it has been proven that inhibition of Drp1 by mdivi-1 improves survival and attenuates cerebral ischemic injury after cardiac arrest. In this study, we compared the effects of Drp1 inhibition with therapeutic hypothermia on post-resuscitation neurologic injury in a rat model of cardiac arrest. Rats were randomized into 4 groups: Mdivi-1 treatment group (n = 39), hypothermic group (n = 38), normothermic group (n = 41), and sham group (n = 12)...
January 8, 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29324234/sphingosine-1-phosphate-mediates-the-therapeutic-effects-of-bone-marrow-mesenchymal-stem-cell-derived-microvesicles-on-articular-cartilage-defect
#7
Chuan Xiang, Kun Yang, Zhiyong Liang, Yulong Wan, Yanwei Cheng, Dong Ma, Heng Zhang, Weiyu Hou, Panfeng Fu
Microvesicles (MVs) are emerging as a new mechanism of intercellular communication by transferring cellular components to target cells, yet their function in disease is just being explored. However, the therapeutic effects of MVs in cartilage injury and degeneration remain unknown. We found MVs contained high levels of sphingosine-1-phosphate (S1P) compared with the original bone marrow mesenchymal stem cells (MSCs). The enrichment of S1P in MVs was mediated by sphingosine kinase 1 (SphK1), but not by sphingosine kinase 2 (SphK2)...
December 15, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29291380/unique-metabolomic-signature-associated-with-hepatorenal-dysfunction-and-mortality-in-cirrhosis
#8
Ayse L Mindikoglu, Antone R Opekun, Nagireddy Putluri, Sridevi Devaraj, David Sheikh-Hamad, John M Vierling, John A Goss, Abbas Rana, Gagan K Sood, Prasun K Jalal, Lesley A Inker, Robert P Mohney, Hocine Tighiouart, Robert H Christenson, Thomas C Dowling, Matthew R Weir, Stephen L Seliger, William R Hutson, Charles D Howell, Jean-Pierre Raufman, Laurence S Magder, Cristian Coarfa
The application of nontargeted metabolomic profiling has recently become a powerful noninvasive tool to discover new clinical biomarkers. This study aimed to identify metabolic pathways that could be exploited for prognostic and therapeutic purposes in hepatorenal dysfunction in cirrhosis. One hundred three subjects with cirrhosis had glomerular filtration rate (GFR) measured using iothalamate plasma clearance, and were followed until death, transplantation, or the last encounter. Concomitantly, plasma metabolomic profiling was performed using ultra-performance liquid chromatography-tandem mass spectrometry to identify preliminary metabolomic biomarker candidates...
December 12, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29287166/intraoperative-optical-coherence-tomography-of-the-human-thyroid-feasibility-for-surgical-assessment
#9
Sarah J Erickson-Bhatt, Kelly J Mesa, Marina Marjanovic, Eric J Chaney, Adeel Ahmad, Pin-Chieh Huang, Z George Liu, Kelly Cunningham, Stephen A Boppart
Thyroid nodules assessed with ultrasound and fine-needle aspiration biopsy are diagnosed as "suspicious" or "indeterminate" in 15%-20% of the cases. Typically, total thyroidectomy is performed in such cases; however, only 25%-50% are found to be cancerous upon final histopathologic analysis. Here we demonstrate optical coherence tomography (OCT) imaging of the human thyroid as a potential intraoperative imaging tool for providing tissue assessment in real time during surgical procedures. Fresh excised tissue specimens from 28 patients undergoing thyroid surgery were imaged in the laboratory using a benchtop OCT system...
December 8, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29274308/the-platelet-phenotype-in-patients-with-st-segment-elevation-myocardial-infarction-is-different-from-non-st-segment-elevation-myocardial-infarction
#10
Rachel A Schmidt, Craig N Morrell, Frederick S Ling, Preya Simlote, Genaro Fernandez, David Q Rich, David Adler, Joe Gervase, Scott J Cameron
It is assumed that platelets in diseased conditions share similar properties to platelets in healthy conditions, although this has never been examined in detail for myocardial infarction (MI). We examined platelets from patients with ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) compared with platelets from healthy volunteers to evaluate for differences in platelet phenotype and function. Platelet activation was examined and postreceptor signal transduction pathways were assessed...
December 2, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29274776/nrf2-p62-autophagy-pathway-and-its-response-to-oxidative-stress-in-hepatocellular-carcinoma
#11
REVIEW
Bartolini Desirée, Dallaglio Katiuscia, Torquato Pierangelo, Piroddi Marta, Francesco Galli
Deregulation of autophagy is proposed to play a key pathogenic role in hepatocellular carcinoma (HCC), the most common primary malignancy of the liver and the third leading cause of cancer death. Autophagy is an evolutionarily conserved catabolic process activated to degrade and recycle cell's components. Under stress conditions, such as oxidative stress and nutrient deprivation, autophagy is an essential survival pathway that operates in harmony with other stress response pathways. These include the redox-sensitive transcription complex Nrf2-Keap1 that controls groups of genes with roles in detoxification and antioxidant processes, intermediary metabolism, and cell cycle regulation...
November 29, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29245016/preferential-myofibroblast-differentiation-of-cardiac-mesenchymal-progenitor-cells-in-the-presence-of-atrial-fibrillation
#12
Elisa Gambini, Gianluca Lorenzo Perrucci, Beatrice Bassetti, Gabriella Spaltro, Giulia Campostrini, Maria Chiara Lionetti, Alberto Pilozzi, Federico Martinelli, Andrea Faruggia, Dario DiFrancesco, Andrea Barbuti, Giulio Pompilio
Atrial fibrillation (AF) is characterized by electrical, contractile, and structural remodeling mediated by interstitial fibrosis. It has been shown that human cardiac mesenchymal progenitor cells (CMPCs) can be differentiated into endothelial, smooth muscle, and fibroblast cells. Here, we have investigated, for the first time, the contribution of CMPCs in the fibrotic process occurring in AF. As expected, right auricolae samples displayed significantly higher fibrosis in AF vs control (CTR) patients. In tissue samples of AF patients only, double staining for c-kit and the myofibroblast marker α-smooth muscle actin (α-SMA) was detected...
November 27, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29154757/macrophage-polarization-and-meta-inflammation
#13
REVIEW
Chuan Li, Maria M Xu, Kepeng Wang, Adam J Adler, Anthony T Vella, Beiyan Zhou
Chronic overnutrition and obesity induces low-grade inflammation throughout the body. Termed "meta-inflammation," this chronic state of inflammation is mediated by macrophages located within the colon, liver, muscle, and adipose tissue. A sentinel orchestrator of immune activity and homeostasis, macrophages adopt variable states of activation as a function of time and environmental cues. Meta-inflammation phenotypically skews these polarization states and has been linked to numerous metabolic disorders. The past decade has revealed several key regulators of macrophage polarization, including the signal transducer and activator of transcription family, the peroxisome proliferator-activated receptor gamma, the CCAAT-enhancer-binding proteins (C/EBP) family, and the interferon regulatory factors...
January 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29121487/risk-of-cardiac-events-in-long-qt-syndrome-patients-when-taking-antiseizure-medications
#14
David S Auerbach, Yitschak Biton, Bronislava Polonsky, Scott McNitt, Robert A Gross, Robert T Dirksen, Arthur J Moss
Many antiseizure medications (ASMs) affect ion channel function. We investigated whether ASMs alter the risk of cardiac events in patients with corrected QT (QTc) prolongation. The study included people from the Rochester-based Long QT syndrome (LQTS) Registry with baseline QTc prolongation and history of ASM therapy (n = 296). Using multivariate Anderson-Gill models, we assessed the risk of recurrent cardiac events associated with ASM therapy. We stratified by LQTS genotype and predominant mechanism of ASM action (Na+ channel blocker and gamma-aminobutyric acid modifier...
January 2018: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29242101/epigenetic-silencing-of-evl-mir-342-in-multiple-myeloma
#15
Zhenhai Li, Kwan Yeung Wong, Godfrey Chi-Fung Chan, Wee-Joo Chng, Chor Sang Chim
miR-342-3p, localized to 14q32, is a tumor suppressor miRNA implicated in multiple cancers. As the promoter region of its host gene, EVL, is embedded in a CpG island, we postulated that miR-342-3p is an intronic miRNA co-regulated with its host gene by promoter DNA methylation in multiple myeloma (MM). By methylation-specific polymerase chain reaction, verified by quantitative bisulfite pyrosequencing, methylation of EVL/miR-342 was absent in all healthy controls (n = 10) and 12 of 15 (80%) human myeloma cell lines (HMCLs), but partially methylated in 3 of 15 (20%) HMCLs, including KMS-12-PE, OCI-MY5, and RPMI-8226R...
November 23, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29232559/cilostazol-a-phosphodiesterase-3-inhibitor-activates-proteasome-proteolysis-and-attenuates-tauopathy-and-cognitive-decline
#16
Ari W Schaler, Natura Myeku
Alzheimer's disease and several variants of frontotemporal degeneration including progressive supranuclear palsy and corticobasal degeneration are characterized by the accumulation of abnormal tau protein into aggregates. Most proteins, including tau, are degraded via the ubiquitin proteasome system, but when abnormal tau accumulates, the function of 26S proteasomes is downregulated. The negative effect of tau aggregates on the function of the proteasome can have deleterious consequences on protein homeostasis and disease progression...
November 23, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29175480/diagnostic-imaging-in-the-management-of-patients-with-metabolic-syndrome
#17
REVIEW
Seo Rin Kim, Lilach O Lerman
Metabolic syndrome (MetS) is the constellation of metabolic risk factors that might foster development of type 2 diabetes and cardiovascular disease. Abdominal obesity and insulin resistance play a prominent role among all metabolic traits of MetS. Because intervention including weight loss can reduce these morbidity and mortality in MetS, early detection of the severity and complications of MetS could be useful. Recent advances in imaging modalities have provided significant insight into the development and progression of abdominal obesity and insulin resistance, as well as target organ injuries...
November 22, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29222967/stimulation-of-the-endogenous-incretin-glucose-dependent-insulinotropic-peptide-by-enteral-dextrose-improves-glucose-homeostasis-and-inflammation-in-murine-endotoxemia
#18
Faraaz Ali Shah, Srikanth Singamsetty, Lanping Guo, Byron W Chuan, Sherie McDonald, Bryce A Cooper, Brett J O'Donnell, Darko Stefanovski, Burton Wice, Yingze Zhang, Christopher P O'Donnell, Bryan J McVerry
Loss of glucose homeostasis during sepsis is associated with increased organ dysfunction and higher mortality. Novel therapeutic strategies to promote euglycemia in sepsis are needed. We have previously shown that early low-level intravenous (IV) dextrose suppresses pancreatic insulin secretion and induces insulin resistance in septic mice, resulting in profound hyperglycemia and worsened systemic inflammation. In this study, we hypothesized that administration of low-level dextrose via the enteral route would stimulate intestinal incretin hormone production, potentiate insulin secretion in a glucose-dependent manner, and thereby improve glycemic control in the acute phase of sepsis...
November 21, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29172034/development-of-mannose-functionalized-dendrimeric-nanoparticles-for-targeted-delivery-to-macrophages-use-of-this-platform-to-modulate-atherosclerosis
#19
Hongliang He, Quan Yuan, Jinghua Bie, Ryan L Wallace, Paul J Yannie, Jing Wang, Michael G Lancina, Olga Yu Zolotarskaya, William Korzun, Hu Yang, Shobha Ghosh
Dysfunctional macrophages underlie the development of several diseases including atherosclerosis where accumulation of cholesteryl esters and persistent inflammation are 2 of the critical macrophage processes that regulate the progression as well as stability of atherosclerotic plaques. Ligand-dependent activation of liver-x-receptor (LXR) not only enhances mobilization of stored cholesteryl ester but also exerts anti-inflammatory effects mediated via trans-repression of proinflammatory transcription factor nuclear factor kappa B...
November 21, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/29175267/the-role-of-macrophage-phenotype-in-regulating-the-response-to-radiation-therapy
#20
REVIEW
Xiaoshan Shi, Stephen L Shiao
Increasing experimental and clinical evidence has revealed a critical role for myeloid cells in the development and progression of cancer. The ability of monocytes and macrophages to regulate inflammation allows them to manipulate the tumor microenvironment to support the growth and development of malignant cells. Recent studies have shown that macrophages can exist in several functional states depending on the microenvironment they encounter in the tissue. These functional phenotypes influence not only the genesis and propagation of tumors, but also the efficacy of cancer therapies, particularly radiation...
November 20, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
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